Anti-HIV drug regimens have dramatically improved the rates of prevention of mother-to-child transmission (MTCT) of HIV in developed countries. However, little is known of the effectiveness of such regimens in developing countries, such as Botswana. This study will determine whether Trizivir (TZV), a single pill containing abacavir sulfate, lamivudine, and zidovudine (ABC/3TC/ZDV), or lopinavir/ritonavir (LPV/r) and lamivudine/zidovudine (3TC/ZDV) is more effective in reducing HIV-1 viral load and preventing MTCT among HIV infected pregnant women in Botswana.

Lopinavir/Ritonavir/Combivir vs. Abacavir/Zidovudine/Lamivudine for Virologic Efficacy and the Prevention of Mother-to-Child HIV Transmission Among Breastfeeding Women With CD4 Counts Greater Than or Equal to 200 Cells/mm3 in Botswana

Time from randomization to the first adverse event requiring discontinuation of any of the drugs that formed the initial regimen by treatment arm and compared to Mashi study [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Time from randomization to the first Grade 3 or higher adverse event by treatment arm and compared to Mashi study [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Comparison of neurodevelopment at 2 years of age in the Mashi study and this study [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Adherence, as measured by questionnaire and pill count [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Occurrence of HIV-1 RNA genetic mutations associated with viral resistance in maternal plasma and breast milk and infant plasma among transmitting mother-infant pairs at the nearest time to transmission [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Antiretroviral therapy (ARV) toxicities and viral load differences by maternal HLA type, for subset of up to 500 women with HLA-type available [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

ARV concentrations in breast milk and serum and in their infants' serum for all transmitting mother-infant pairs and a matched group of nontransmitting pairs [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Participants in Arm 1A will have CD4 counts of 200 cells/mm3 or more and will receive TZV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV.

Participants in Arm 1B will have CD4 counts of 200 cells/mm3 or more and will receive LPV/RTV and 3TC/ZDV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV.

Drug: Lamivudine/Zidovudine

150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily

Other Names:

3TC/ZDV

Combivir

Drug: Lopinavir/Ritonavir

400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily

Other Name: LPV/RTV

Experimental: 2

Participants in Arm 2 will have CD4 counts less than 200 cells/mm3 and will receive NVP once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group.

Drug: Nevirapine

200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily

Other Name: NVP

Detailed Description:

While perinatal HIV infection has become rare in developed countries through the use of highly active antiretroviral therapy (HAART), it remains a serious problem in developing countries. Botswana has a population of approximately 1.7 million; the prevalence of HIV in Botswana is about 37.4%. In the developed world, HAART has revolutionized the prevention of MTCT among nonbreastfed infants. This trial will compare the effectiveness of a protease inhibitor (PI)-based regimen versus a triple nucleoside reverse transcriptase inhibitor (NRTI)-based regimen in preventing MTCT of HIV.

This study will last up to 24 months for mothers and their children. Participants will be stratified based on their CD4 count at screening. Women with CD4 counts of 200 cells/mm3 or more will be in one of two treatment groups and will be randomly assigned to receive either TZV twice daily or LPV/RTV and 3TC/ZDV twice daily. Once in labor, treatment group participants will continue to take their assigned HAART regimen and will also be given additional ZDV. Women with CD4 counts less than 200 cells/mm3 will receive nevirapine (NVP) once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group.

Shortly after birth, infants will receive single-dose NVP. A 1-month supply of ZDV will be provided to the mother to administer daily to her child. Mothers will stop HAART at 6 months postpartum or when they stop breastfeeding, whichever occurs earlier. A clinical evaluation, blood collection, and HIV prevention counseling will occur at all maternal visits. An obstetrical exam and physical exam will occur at selected visits. Women will provide at least four samples of breast milk during the first 5 months postpartum. For infants, a clinical evaluation will occur at every visit, and a physical exam and blood collection will occur at selected visits.

Eligibility

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria for Mothers:

HIV-infected

At least at 26th week of pregnancy (treatment group) or 18th week of pregnancy (observational group) but not beyond the 34th week of pregnancy

Able to complete study visits until at least 6 months postpartum

Citizen of Botswana

Exclusion Criteria for Mothers:

Taken ARVs for more than 1 week, other than ZDV, during current or prior pregnancy. Women who have received single-dose NVP in a prior pregnancy are not excluded.

Certain abnormal laboratory values

Plan to formula feed

Known fetal abnormalities that suggest the fetus will not survive to 6 months of gestational age

Known allergy or medical contraindication to any of the study drugs

Require certain medications

Previous participation in the "Prevention of Milk-Borne Transmission of HIV-1C in Botswana" (Mashi) study

Currently incarcerated

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270296